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Histamine H1 receptor deletion in cholinergic neurons induces sensorimotor gating ability deficit and social impairments in mice

Research group Swaab
Publication year 2021
Published in Nature Communications
Authors Li Cheng, Cenglin Xu, Lu Wang, Dadao An, Lei Jiang, Yanrong Zheng, Yixin Xu, Yi Wang, Yujing Wang, Kuo Zhang, Xiaodong Wang, Xiangnan Zhang, Aimin Bao, Yudong Zhou, Jingyu Yang, Shumin Duan, D.F. Swaab, Weiwei Hu, Zhong Chen

Negative symptoms in schizophrenia strongly contribute to poor functional outcomes, however its pathogenesis is still unclear. Here, we found that histamine H1 receptor (H1R) expression in basal forebrain (BF) cholinergic neurons was decreased in patients with schizophrenia having negative symptoms. Deletion of H1R gene in cholinergic neurons in mice resulted in functional deficiency of cholinergic projections from the BF to the prefrontal cortex and in the formation of sensorimotor gating deficit, social impairment and anhedonia-like behavior. These behavioral deficits can be rescued by re-expressing H1R or by chemogenetic activation of cholinergic neurons in the BF. Direct chemogenetic inhibition of BF cholinergic neurons produced such behavioral deficits and also increased the susceptibility to hyperlocomotion. Our results suggest that the H1R deficiency in BF cholinergic neurons is critical for sensorimotor gating deficit, social impairments and anhedonia-like behavior. This finding may help to understand the genetic and biochemical bases of negative symptoms in schizophrenia.

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